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Carcinoma Esophagus - Surgical trials.pptx

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Carcinoma Esophagus - Surgical trials.pptx

  1. 1. PROF S.SUBBIAH et al. Carcinoma Esophagus - Surgical trials
  2. 2. PROF S.SUBBIAH et al. • The main goal of surgery in esophageal cancer was good palliation and the cure is an accident. - Ronald H. Belsey (1910-2007)
  3. 3. PROF S.SUBBIAH et al. History • First excision of Esophagus is done by Christian Albert Theodor Billroth, an Austrian surgeon -1872 • Vincenz Czerny (1842-1916) performed the first successful human resection of cervical Esophagus in 1877 where he had resected a carcinoma of cervical Esophagus that provided patient a one year survival.
  4. 4. PROF S.SUBBIAH et al. • A Major pioneer in esophageal surgery was Ivor Lewis (1895 to 1982) who in 1946 made a substantial advancements with the introduction of esophagectomy and esophagogastrostomy • Surgery has normally been considers the only option for patients with early stage cancer of Esophagus until the mid 1980s, later that other combined modality options became available to patients
  5. 5. PROF S.SUBBIAH et al. Treatment of Premalignant Disease • Photodynamic laser • Multipolar Electro coagulation • argon plasma coagulation • Cryotherapy • Radio frequency ablation
  6. 6. PROF S.SUBBIAH et al. • A RCT of 127 Overall, • 77.4% of patients in the ablation group had complete eradication of intestinal metaplasia, as compared with 2.3% of those in the ( PLACEBO) control group (P<0.001). • Patients in the ablation group had less disease progression (3.6% vs. 16.3%, P=0.03) and fewer cancers (1.2% vs. 9.3%, P=0.045).
  7. 7. PROF S.SUBBIAH et al. Chance of lymphnode involvement • m1 and m2 is 0% • m3 8% • sm1 17% ( <200 micro meter thickness) • sm2 30%
  8. 8. PROF S.SUBBIAH et al. Endoscopic resection SIZE < 2cm Not poorly differentiated No Nodal involvement Lesion thickness not beyond sm1
  9. 9. PROF S.SUBBIAH et al. EMR or ESD for superficial esophageal cancer • EMR for lesions < 2cm/ ESD for >2cm • Pooled R0 resection rate – 90% • If tumor > 2.5cms – R0 resection rate is 85% • 5 year recurrence rate – EMR (23%) vs ESD (2.9%)
  10. 10. PROF S.SUBBIAH et al. •If the disease is extensive, or pT1b(sm2,sm3) esophagectomy is recommended
  11. 11. PROF S.SUBBIAH et al. NCCN Guidelines • Esophagectomy is recommended primary treatment option for patients with pT1b,N0 tumours and cT2,N0 low risk lesions ( <3cm in diameter and well- differentiated)
  12. 12. PROF S.SUBBIAH et al. NCCN guidelines • Preoperative Chemoradiation ( for Non cervical Esophagus) and definitive Chemoradiation ( for cervical Esophagus) are recommended for patients with cT2,N0 high risk lesions ( LVI, >3cm, poorly differentiated) and cT1b-cT2, N+ or cT3-cT4a, any N tumours
  13. 13. PROF S.SUBBIAH et al. Transhiatal Esophagectomy • En-bloc resection is feasible for distal esophageal tumors • Laparotomy and cervical approach • Peritumoral or two field lymph node dissection ( Abdominal and lower mediastinal) • Cervical anastomosis
  14. 14. PROF S.SUBBIAH et al.
  15. 15. PROF S.SUBBIAH et al.
  16. 16. PROF S.SUBBIAH et al. • N – 1525 patients • 79% of them had Adeno carcinoma • Tumors located in lower third Esophagus in 82%, middle and upper third in 18% • In hospital mortality was 3% • Most common complication was anastomotic leak (12%), Recurrent laryngeal nerve palsy (4.5%) • 5 year OS was 29%
  17. 17. PROF S.SUBBIAH et al.
  18. 18. PROF S.SUBBIAH et al.
  19. 19. PROF S.SUBBIAH et al. Transthoracic Esophagectomy
  20. 20. PROF S.SUBBIAH et al.
  21. 21. PROF S.SUBBIAH et al.
  22. 22. PROF S.SUBBIAH et al.
  23. 23. PROF S.SUBBIAH et al. • Pulmonary complications are more or less same • 5 year overall survival was similar – 24% for transhiatal esophagectomies and 26% for transthoracic esophagectomies
  24. 24. PROF S.SUBBIAH et al.
  25. 25. PROF S.SUBBIAH et al.
  26. 26. PROF S.SUBBIAH et al.
  27. 27. PROF S.SUBBIAH et al.
  28. 28. PROF S.SUBBIAH et al. • 30 day mortality high in trans thoracic group ( 10.6% vs 7.2%) as was the pulmonary complications and length of stay ( 4days more) • Anastomotic stricture and vocal cord palsy was significantly higher in transhiatal group • 5 year OS was not statistically different 26.6% in transthoracic and 25.8% in trans hiatal group
  29. 29. PROF S.SUBBIAH et al.
  30. 30. PROF S.SUBBIAH et al.
  31. 31. PROF S.SUBBIAH et al.
  32. 32. PROF S.SUBBIAH et al. • New update from the author showed OS 34% in transhiatal and 36% in transthoracic resection – though lymphnode retrieval is more in trans thoracic esophagectomy
  33. 33. PROF S.SUBBIAH et al. Minimally invasive esophagectomy
  34. 34. PROF S.SUBBIAH et al. • MIE can be performed safely with an overall operative mortality of 1.68% • a median ICU stay of 2 days, and a median hospital stay of 8 days. • The morbidity of the procedure was acceptable and similar to or better than most published series of open esophagectomy.
  35. 35. PROF S.SUBBIAH et al. • In preliminary comparison of outcomes between the MIE- neck and MIE-chest groups, median length of ICU and hospital stay, overall morbidity, and operative mortality seemed to be similar between the 2 approaches. • The 30-day mortality was 0.9% in the MIE Ivor Lewis group and 2.5% in the MIE-Neck group. • The incidence of recurrent laryngeal nerve (RLN) injury was significantly lower in the Ivor Lewis MIE-chest group (1%) than in the MIE-Neck group (P < 0.001).
  36. 36. PROF S.SUBBIAH et al. TIME trial
  37. 37. PROF S.SUBBIAH et al. • 115 patients were randomly assigned to minimally invasive esophagectomy and open esophagectomy with the primary endpoint of post operative infections within 2 weeks of surgery • Minimally invasive group were associated with statistically significant reduction pulmonary infections 9% vs 29% and and also in hospital pulmonary infections were less in MIE ( 12% vs 34%) • Hospital stay ( 11 vs 14 days) • there was no difference detected in 30 days or in hospital mortality and post operative complications rate were similar
  38. 38. PROF S.SUBBIAH et al. • in-hospital mortality, one patient in the open esophagectomy group died from anastomotic leakage and two in the minimally invasive group from aspiration and mediastinitis after anastomotic leakage.
  39. 39. PROF S.SUBBIAH et al.
  40. 40. PROF S.SUBBIAH et al.
  41. 41. PROF S.SUBBIAH et al.
  42. 42. PROF S.SUBBIAH et al.
  43. 43. PROF S.SUBBIAH et al. • A reduction in in hospital mortality (3% vs 4.6%) • Pulmonary complications 17.8% vs 20.4 • Other complications are more or less same • Conclusion: MIE is superior to open esophagectomy
  44. 44. PROF S.SUBBIAH et al. Real world data
  45. 45. PROF S.SUBBIAH et al.
  46. 46. PROF S.SUBBIAH et al.
  47. 47. PROF S.SUBBIAH et al. JCOG 1409 • JAPAN is conducting a RCT with n=300 patients • End point is Overall survival • This is largest trial with survival as outcome in the debate between MIE vs open esophagectomy
  48. 48. PROF S.SUBBIAH et al. • Minimally invasive esophagectomy is the ideal approach to operate esophageal cancer • Reduced morbidity with equivalent oncological outcomes • No difference in routine community practice
  49. 49. PROF S.SUBBIAH et al.
  50. 50. PROF S.SUBBIAH et al. Extended esophagectomy
  51. 51. PROF S.SUBBIAH et al.
  52. 52. PROF S.SUBBIAH et al. • 174 patients underwent 3 field lymphadenectomy • A total of 23% of patients with adenocarcinoma and 25% of those with SCC had positive cervical nodes • 5 year survival for patients with positive cervical nodes was 27% for SCC And 12% in adenocarcinoma patients
  53. 53. PROF S.SUBBIAH et al. • Authors suggest that 3 field lymphadenectomy may have a role in patients with SCC and this remains investigational for patients with adenocarcinoma
  54. 54. PROF S.SUBBIAH et al.
  55. 55. PROF S.SUBBIAH et al.
  56. 56. PROF S.SUBBIAH et al. TATA MEMORIAL
  57. 57. PROF S.SUBBIAH et al. Palliation
  58. 58. PROF S.SUBBIAH et al. TROG 03.01NCIC CTG ES2
  59. 59. PROF S.SUBBIAH et al. DUTCH SIREC study group
  60. 60. PROF S.SUBBIAH et al.
  61. 61. PROF S.SUBBIAH et al. • If patient requires rapid palliation – laser or stent placement are recommended • EBRT with or without Chemotherapy takes at least 2 weeks to produce palliation, but once palliation is achieved it is more durable
  62. 62. PROF S.SUBBIAH et al. Thank You…..!

Notas do Editor

  • Because 5 year survival rates are just touching 20%
  • High grade dysplasia in barrets – most powerful predictor of subsequent invasive adenocarcinoma and is associated with a per year cancer incidence of 6%, therefore warranting therapeutic intervention
    But esophagectomy is extra kill– most of them do not develop invasive carcinoma in life time
    Which led to use of these endoscopic methods to cure
    eliminate mucosa at risk
    All of these techniques cause destruction of mucosal layer. RFA is considered as preferred ablative technique
  • once the lesion goes into sm1 chance of Lymphnode involvement is high
    So till sm1 can try endoscopic resection
  • Localised resectable carcinoma
    Surgery is the treatment of choice
  • Locally advanced cancers
  • Recently gained popularity in USA with increasing incidence of adenocarcinoma
    Division of diaphragmatic crus allows wide access to the mediastinum and dissection under vision of middle and lower third of Esophagus
    A left cervical incision to mobilise upper thoracic Esophagus
    We preserve right gastroepiploic and right gastric vessels on whose pedicle reconstructive conduit will be based
  • Shorter duration of operation
    Main advantage of transhiatal esophagectomy include avoidance of thoracotomy incision which there by minimizes pain and subsequent pulmonary complications
    Lethal complications like mediastinitis associated with an intrathoracic anastomotic leak is avoided
  • 2007
  • Leak was managed simply by opening the wound and local care
    Among this 185 patients who has leak 81(44%) has undergone Neoadjuvant chemoradiation
    Hoarseness settled spontaneously in 99% of cases in 2 to 12 wk, Less than 1% needed cord medialisation
    Chylothorax in 1% managed successfully by transthoracic ligation of the thoracic duct
  • Stage specific survival was 65% for Stage 1, 28% for stage II, 29% for stage IIB and 11% for stage III
  • A right thoracotomy and a upper midline laparotomy ( ivor lewis) is most common procedure used for esophageal resection
    Right thoracotomy through 5th or 6Th ICS, azygous vein is divided, mediastinal pleura incised, the intrathoracic Esophagus mobilizesd and mediastinal nodes mobilised
    Under direct visualization more adequate radial margin and more thorough lymph node dissection is possible( theoretically oncologically more sound)
    Old age with comorbidities – this may compromise cardiorespiratory function
    An intrathoracic anastomosis leak can lead to medistinitis, sepsis and death – 3 incision modification effectively potential complications associated with intra thoracic esophago gastric anastomosis
  • a meta analysis published in 1999
    44 studies
  • 44 series ( published between 1986 – 1996
    Other parameters are more or less same
    Perioerative mortality was significantly higher in transthoracic esophagectomy group than in the thanshiatal group
  • Pulmonary complications are more or less same
    Cardiac complications are a bit higher in trans hiatal groupjh
    5 year overall survival was similar – 24% for transhiatal esophagectomies and 26% for transthoracic esophagectomies
  • 2000- hulscher et al , A bigger meta analysis
    50 studies
    3 RCT
    6 prospective trials
    18 retrospective comparative trials
    15 series of TTE
    11 series of THE
  • Cardiac complications are more in THE , may be due to blind mobilisation of Esophagus
    if u take only RCT into consideration cardiac and pulmonary complications are same in THE and TTE

    In TTE also leak rates are more with mc keowns than with ivoe lewis, as stomach travels a shorted distance so it will be more vascular
  • 5 year OS 21.7 in transhiatal group compared to 23% in transthoracic group
  • It included 50 studies, it included studies till 2010
    30 day mortality high in trans thoracic group ( 10.6% vs 7.2%) as was the pulmonary complications and length of stay ( 4days more)
    Anastomotic stricture and vocal cord palsy was significantly higher in transhiatal group
    5 year Os was not statistically different 26.6% in transthoracic and 25.8% in trans hiatal group
  • This trial from Netherlands deserves a special mention
    220 patients
    Trans thoracic group underwent a systematic mediastinal and upper abdominal lymphnode dissection, although the no of LNs retrieved in transthortacxic group is high (31 vs 16)
    there is no difference in the radicality of the procedure
  • New update from this author showed OS 34% in transhiatal and 36% in transthoracic resection – though lymphnode retrieval is more in trans thoracic esophagectomy
    In esophageal cancers when u did a TTE (51%) there is 14% increase OS compared to THA (37%)
    Authors concluded that TTE for esophageal and THE for junctional and cardiac cancers
    Either it may be transhiatal or trans thoracic can be performed with acceptable morbidity and mortality and out comes are remarkably similar
  • Either it may be transhiatal or trans thoracic can be performed with acceptable morbidity and mortality and out comes are remarkably similar
  • In an attempt to reduce morbidity and mortality while achieving an equivocal oncological outcome, minimally invasive esophageal resection have been designed and continued to be investigated
    Variety of these including laparoscopic, thoracoscopic, lap and thoracoscopic combined, hand assisted, robotic assisted were being studied
    Largest single institutional study has been reported by Luketich et al 2012 which included 1011 patients
  • Stage specific survival was similar to series with open esophagectomies
    Results from this study where promising an impressive but whether the reproducible in other institutions need to be determined through further study
  • The first multicentre( Netherlands) randomised controlled trail of minimally invasive esophagectomy versus open esophagectomy recently reported its short term results
  • R0 resection rates and lymphnode retrieval were equivalent
  • There is no difference in 3yr OS and DFS
    One can reasonably conclude that MIE is safe when compared to open esophagectomy and MIE may be non inferior to open esophagectomy
    although large multicentre randomized trails would be valuable
  • Meta analysis
  • 48 studies
    Most of them are again retrospective or prospective non RCTs
    Over all complications in this has favoured MIE
  • Marten et al Netherlands
    Explanation for high gastric conduit necrosis: ? Higher use of energy devices, and going close to gastric wall, harsher handling of gastric tube with instruments compared to hand
    Needs to be investigated
  • Accrural is going on
  • China 6 high vol centers
    With robot shorter time of surgery, improved efficacy of LN dissection
    No diff in blood loss, R0 resections
    Peri op complications are same
    OS data is yet to come out
  • It involves resection of middle and lower esophageal tumors with an envelope of adjacent tissue that includes the mediastinal pleura laterally, pericardium anteriorly, azygous vein and thoracic duct postero-laterally with surrounding periesophageal tissue and lymph nodes
    For tumors traversing esophageal hiatus, a cuff of diaphragm is resected
  • Lerut et al
    Authors suggest that 3 field lymphadenectomy may have a role in patients with SCC and this remains investigational for patients with adenocarcinoma
    Extended resections may improve staging and may enhance locoregional control how ever no reliable data confirming a survival benefit of these procedures
  • Not much survival benefit
    ever no reliable data confirming a survival benefit of these procedures
  • Options of palliation include stents, feeding tubes, CT, EBRT, brachytherapy or combination of all these procedures
    Harvey et al treated 106 patients with CTRT and reported 78% had improvement of at least one grade in their dysphagia score, and 51% maintained swallowing improvement until time of last follow up
  • A recent phase 3 randomised trial conducted in UK, Canada, Australia and NZ – they compared palliation with RT vs CTRT
    220 patients were randomized
    35 Gy EBRT vs EBRT with cisplatin and 5FU
    Dysphagia was measured with using several QOL instrument and common terminology criteria for adverse events
    No difference in dysphagia response but high GI toxicities in CTRT arm, median survival is 210 in CTRT vs 203 in RT arm
    However 10% of all there patients were alive at 2yrs indicating that this group should not be denied some active cancer treatment
  • Endoluminal brachy is also an effective method in achieving palliation but limited availability
    Stent vs 12 Gy brachy
    Dysphagia improved more rapidly after stent placement how ever long term relief was with Brachytherapy
  • Major limitation with brachy is it can treat disease only up to 1cm from source, >1cm suboptimal response
    So brachy is not as successful as EBRT in treating entire tumor volume
    Rosenblatt et al reported in their multi institutionsl phase 3 RCT
    HDR brachy vs Brachy with EBRT
    Dysphagia was significantly improved with combined therapy and there is no difference in toxicities and OS
  • Because EBRT treats tumor not just symptom

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